The non-invasive diagnosis of human glioma could improve the quality of life of patients with this disease by allowing patients to be directly diagnosed or stratified for treatment without the need of an invasive brain biopsy. In this study, the investigators propose to develop novel extracellular RNA biomarkers for the diagnosis of human glioma tumors. Using a prioritized panel of tumor specific extracellular RNA (exRNA) genetic changes, we will test different competing technologies (qPCR, digital PCR, exome sequencing, and DMR) for detecting exRNA candidate biomarkers in blood and CSF of glioma patients. In the UH3 phase of study, we will create a consortium of institutions to provide rapid prospective collection of tumor tissue CSF, and blood from glioma patients and establish common protocols for CSF and blood collection to support clinical diagnostic glioma exRNA assays. We will then validate the diagnosis of glioma by exRNA using blood or CSF exRNA assays (as prioritized from the UH2 phase) and tested in two clinical patient population; 1) suspected low grade and 2) suspected high grade glioma. Prototypical markers that will be tested will include the detection of IDH1 mutations in low grade tumors and EGFRvIII in high grade tumors. We anticipate the ability to determine the sensitivity and specificity with which a CSF or blood test can be used to diagnosis human glioma. We further anticipate that in patients with difficult to biopsy tumors, the results o this study will yield a method for diagnosing brain tumors non-invasively thus reducing the need for invasive brain surgery and appropriately stratifying patients for targeted therapies.